Though equine skin cancers are usually fairly easy to identify, internal cancers can be significantly more difficult to diagnose. Clinical symptoms are often vague, like weight loss and fever, while testing for known biomarkers is not ideal as many other factors can influence their concentrations.

Blood work, diagnostic imaging, endoscopic exams, and rectal palpation are often used to help make a definitive diagnosis. Other effective diagnostic tools include advanced imaging, like the use of a CT machine, and biopsies. Peritoneal and pleural fluids may be examined as well, but those results are not concrete. Bloodwork results may indicate organ dysfunction, but it is rarely specific enough. Cancer cells can induce paraneoplastic syndromes, in which substances are produced that cause secondary changes to blood work or physical signs. Measuring these circulating substances, called tumor markers, can help diagnose the type of cancer and its stage; it can also be helpful in monitoring cancer treatment and disease control.  There are three main types of internal tumor markers: hormones, enzymes, and antibodies. Scientists at the Free University of Berlin performed a review seeking to describe the tumor markers available in equine medicine, as well as the factors influencing their concentration or activity. They concluded that none of the known tumor markers is an ideal biomarker; factors like age, pregnancy, inflammation, infection, or lactation can increase the concentration or activity of these biomarkers. To avoid false positive diagnoses, test results should be examined alongside the horse’s history, clinical signs, and lab results. Ongoing testing is also advised; as tumors typically progress, the results should follow suit.